Figure 6

Diagram showing the possible mechanism of Infliximab in the porcine retinal degeneration model. PDE6 inhibition induces cGMP accumulation and triggers retinal degeneration. The degeneration is accompanied by upregulation of inflammatory mediators, PARP pathway, reactive gliosis and oxidative stress markers. According to the current study, TNFΑ may be involved in the retinal degeneration by increasing caspase-3 activation and reactive gliosis. Infliximab may prevent cell death by inhibiting caspase-dependent pathways that converge in caspase-3 activation in the INL. Infliximab also may prevent cell death by caspase-independent pathways that remain unclear in the ONL and GCL. Moreover, Infliximab may exacerbate PARP over activation probably through the caspase-3 inhibition. This over activation could contribute to the future cell death. cGMP: cyclic GMP; GCL, ganglion nuclear layer; GFAP: glial fibrillary acidic protein; INL, inner nuclear layer; NO: nitric oxide; ONL, outer nuclear layer; PAR: poly(ADP-ribose) polymers; PARG: poly(ADP-ribose) glycohydrolase; PARP: poly(ADP)ribose polymerase; PDE6: phosphodiesterase 6; TAC: total antioxidant capacity; TBARS: thiobarbituric acid reactive substances; TNFΑ: tumor necrosis factor alpha.